Jeffrey Gray is a microbiologist whose research focuses on severe bacterial infections. Gray’s research and interests include antibiotic resistance, foodborne infections and sepsis. He currently has projects exploring the pathogenesis of multiple drug resistantSalmonella and E. coli, detection of methicillin resistant Staphylococcus aureus (MRSA) and developing alternative approaches for treatment of septicemias. Gray’s research has been key to understanding the transmission of multiple drug resistant Salmonella and development of a rapid method to detect MRSA.

Using pigs as a model for multiple drug resistant Salmonelladissemination

Drug resistance in pathogens is a global problem in human and animal healthcare. Moreover, this problem has been compounded by the occurrence of multi-drug resistance in a number of pathogens. Salmonellathat are resistant to ceftriaxone have usually acquired a plasmid on which the blaCMY-2 gene is carried. This gene is alwayscarried on large multi-drug resistant plasmids that are usually self transferable by conjugation and which also may mediate resistance to non beta-lactam antimicrobials such as tetracycline, gentamicin, streptomycin, sulphonamides, and chloramphenicol. We have experimented with the effect of tetracycline on the dissemination of two Salmonella Typhimurium strains in pigs and the effect of the multiple-drug resistant CMY-2 plasmid on a pan-sensitive Salmonella Typhimurium strain.

The Salmonella Typhimurium inoculum was orally administered to one pig in each pen and qualitative and quantitative measurements of colonization and shedding were taken over a seven-day period. Pens were either treated with blaCMY-2 positive or blaCMY-2 negative Salmonella Typhimurium strains, and also received either tetracycline treatment or not. There was no statistically significant difference in dissemination ofSalmonella among pigs in the tetracycline treated and non-treated pens. However there was a significantly higher level of colonization and shedding in pigs treated with the blaCMY-2positive Salmonella Typhimurium strain compared to the pigs treated with the blaCMY-2negative Salmonella Typhimurium strain. This research is indicative of the potential for increased spread among these isolates.

Alternative approaches to sepsis treatment

As the tenth leading cause of death in the United States and the number one cause of death in non-cardiac intensive care units, sepsis is a serious health concern. Despite broad advances in infectious disease control, the incidence of sepsis has only increased. Gram-positive bacteria, mainly Staphylococcus epidermidis andStaphylococcus aureus, are among the leading organisms causing sepsis. Recent epidemiologic studies have indicated a possible association between routine statin drug use for the management of dyslipidemias and a decreased risk of sepsis-related morbidity and mortality. Many have ascribed this effect to the immunomodulatory effects of statins on the host immune system, while some have attributed it to a direct antimicrobial effect of statins. This study explores the effect of atorvastatin, fluvastatin, and simvastatin on the growth parameters of Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-sensitive Staphylococcus aureus (MSSA). By using a microtitre dilution method and generating unrestricted bacterial growth curves, this work shows that there is no significant direct antimicrobial effect of statins. However, further analysis indicated that certain statins do have an inhibitory effect on the unrestricted growth of these organisms. Simvastatin and atorvastatin in particular were observed to significantly reduce the optical density of bacteria growing in culture. Additionally, these statin-mediated inhibitory effects also increased the generation time of the bacterial pathogens. Therefore, statins clearly affect the unrestricted growth and generation time of gram-positive bacteria, but do not exert a direct antimicrobial effect. However, neither mevalonate nor mevalonolactone could restore normal growth in the presence of statins that showed an inhibitory effect on the unrestricted bacterial growth curve. This indicates that the effects observed may not be due to an interaction of the statin with the class II bacterial HMG-CoA reductase, which is similar to the eukaryotic HMG-CoA reductase that is the target of statin drugs. These results are indicative that specific statins have a direct interaction with bacterial pathogens involved in sepsis. Statin-induced alteration or limitation of bacterial growth in the bloodstream could be a contributing mechanism to the statin associated reduction in sepsis-related morbidity and mortality that has been reported.

2011 research

We are interested in the analysis of multiple drug resistant organisms including Salmonella, E-coli, MRSA and Enterococci. We explore host-pathogen interactions as they relate to strategies to exclude and control pathogens and reduce infections. We have collaborative efforts to examine pathogen prevalence and transmission between hosts and between animals and humans.